This proposal focuses on elucidation of biochemical, physiological, and structural aspects of bacterial RNA polymerase role as a genome-wide DNA damage surveillance vehicle and resolution of its collisions with replisome. Retrograde movement of RNA polymerase, known is backtracking, has been shown to play crucial role in both processes. We have identified several important RNA polymerase-associated factors, particularly UvrD helicase and GreA/B cleavage factors, that stimulate or antagonize backtracking, and have tremendous impact on cell resistance to genotoxic substances. Here we propose a comprehensive set of biochemical, biophysical, genetic, genomics, and structural proteomics experiments aiming at in-depth investigation of all aspects, from molecular to cellular, of this spectrum of transcription-related phenomena.